title: Vascular pathology of medial arterial calcifications in NT5E deficiency: implications for the role of adenosine in pseudoxanthoma elasticum.
abstract: Arterial Calcification due to Deficiency of CD73 (ACDC) results from mutations in the NT5E gene encoding the 5' exonucleotidase, CD73. We now describe the third familial case of ACDC, including radiological and histopathological details of the arterial calcifications. The medial lesions involve the entire circumference of the elastic lamina, in contrast to the intimal plaque-like disease of atherosclerosis. The demonstration of broken and fragmented elastic fibers leading to generalized vascular calcification suggests an analogy to pseudoxanthoma elasticum (PXE), which exhibits similar histopathology. Classical PXE is caused by deficiency of ABCC6, a C type ABC transporter whose ligand is unknown. Other C type ABC proteins transport nucleotides, so the newly described role of adenosine in inhibiting vascular calcification, along with the similarity of ACDC and PXE with respect to vascular pathology, suggests that adenosine may be the ligand for ABCC6.
authors.affiliation: NIH Undiagnosed Diseases Program, Office of Rare Disease Research and National Human Genome Research Institute and NIH Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. markellot@mail.nih.gov
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Markello
authors.forename: Laura K
authors.initials: LK
authors.lastname: Pak
authors.forename: Cynthia
authors.initials: C
authors.lastname: St Hilaire
authors.forename: Heidi
authors.initials: H
authors.lastname: Dorward
authors.forename: Shira G
authors.initials: SG
authors.lastname: Ziegler
authors.forename: Marcus Y
authors.initials: MY
authors.lastname: Chen
authors.forename: Krishna
authors.initials: K
authors.lastname: Chaganti
authors.forename: Robert L
authors.initials: RL
authors.lastname: Nussbaum
authors.forename: Manfred
authors.initials: M
authors.lastname: Boehm
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D015720:5'-Nucleotidase / Q000172:deficiency* / Q000235:genetics; D000241:Adenosine / Q000378:metabolism*; D000328:Adult; D001158:Arteries / Q000473:pathology*; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000172:deficiency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D011561:Pseudoxanthoma Elasticum / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D011859:Radiography
chemical_list: D058851:GPI-Linked Proteins; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D000241:Adenosine